Cited by 718Cancer, Lipids, and MetabolismLipid metabolism and biosynthesisSphingolipid Metabolism and Signaling

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Fatty acid synthesis: a potential selective target for antineoplastic therapy

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Kuhajda, F P, Jenner, K, Wood, F D, Hennigar, R A, Jacobs, L B, Dick, J D, Pasternack, G R·1994·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.91.14.6379PMC PMC44205

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Abstract

OA-519 is a prognostic molecule found in tumor cells from breast cancer patients with markedly worsened prognosis. We purified OA-519 from human breast carcinoma cells, obtained its peptide sequence, and unambiguously identified it as fatty acid synthase through sequence homology and enzymology. Tumor fatty acid synthase is an approximately 270-kDa polypeptide which specifically abolished immunostaining of human breast cancers by anti-OA-519 antibodies. Tumor fatty acid synthase oxidized NADPH in a malonyl-CoA-dependent fashion and synthesized fatty acids composed of 80% palmitate, 10% myristate, and 10% stearate from acetyl-CoA, malonyl-CoA, and NADPH with a specific activity of 624 nmol of NADPH oxidized per min per mg. Tumor cell lines with elevated fatty acid synthase showed commensurate increases in incorporation of [U-14C]acetate into acylglycerols demonstrating that fatty acid synthase increases occur in the context of overall increases in endogenous fatty acid synthesis. Cerulenin inhibited acylglycerol synthesis in tumor cells and fibroblast controls in a dose-dependent fashion and also caused a growth inhibition which generally paralleled the level of endogenous fatty acid synthesis. Supraphysiologic levels of palmitate, 14 microM in dimethyl sulfoxide, significantly reversed the growth inhibition caused by cerulenin at concentrations of up to 5 micrograms/ml, indicating that cerulenin-mediated growth inhibition was due to fatty acid synthase inhibition.

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Authors: Kuhajda, F. P., Jenner, K., Wood, F. D., Hennigar, R. A., Jacobs, L. B., Dick, J. D., & Pasternack, G. R.
Affiliations: Johns Hopkins University (US)
ORCID: Hennigar, R A
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1994-07-05
Volume: 91
Issue: 14
Pages: 6379-6383
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.91.14.6379
PMC: PMC44205
OpenAlex: W2090846942
Cited by: 705
References: 26
Citations by year: 2026: 13 · 2025: 13 · 2024: 12 · 2023: 32 · 2022: 33 · 2021: 30 · 2020: 19 · 2019: 29 · 2018: 18 · 2017: 31 · 2016: 39 · 2015: 28 · 2014: 38 · 2013: 33 · 2012: 36
FWCI: 3.94
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords: fatty acid synthase, breast cancer, cerulenin, antineoplastic therapy, fatty acid synthesis, palmitate, NADPH oxidation, malonyl-CoA, tumor growth inhibition
MeSH terms: Acetates, Antibodies, Antigens, Neoplasm, Blood Proteins, Breast Neoplasms, Carbon Radioisotopes, Cell Division, Cell Line, Cerulenin, Fatty Acids, Female, Haptoglobins, Humans, Immunohistochemistry, Kinetics, Malonyl Coenzyme A, Palmitic Acids, Prognosis, Tumor Cells, Cultured, Biomarkers, Tumor, Drug Design, Palmitic Acid, Fatty Acid Synthases

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Fatty acid synthesis: a potential selective target for antineoplastic therapy

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